Cancer survival statistics establish the importance of early detection and thorough tumor resection for maximization of patient lifespan. Recent efforts to better achieve these objectives have focused on development of safer, more sensitive, and more discriminating imaging methodologies. MRI techniques rely on differences in water relaxivity between malignant lesions and healthy cells to achieve the desired contrast. PET imaging and methodologies generally exploit differences in metabolic fluxes between cancer and normal cells to allow tumor visualization. Some radiological imaging methods rely on the elevated passive vascular permeability of many neoplasms to achieve contrast with healthy tissues. Whereas radiological and magnetic resonance imaging modalities have clearly led the field in early detection, increased interest has arisen in developing optical imaging techniques for tumor diagnosis, largely because of safety concerns with the routine use of other methodologies.
Described herein is a method of use for a tumor targeting ligand, the vitamin folic acid, by which folic acid delivers optical probes to both primary and metastatic tumors overexpressing the folate receptor. Furthermore, an apparatus is disclosed to allow viewing of the tumor both excised and in-vivo. Upon laser excitation, derived images of normal tissues generally show little or no fluorescence, whereas images of folate receptor-expressing tumors display bright fluorescence that can be easily distinguished from adjacent normal tissue with the naked eye. Further, with the aid of appropriate optics, metastatic tumor loci of submillimeter size can also be visualized. The sharp distinction between tumor and normal tissues enabled by this technique finds application in the localization and resection of tumor tissue during surgery or in the enhanced endoscopic detection and staging of cancers.
According to a first embodiment of the present invention, a method of differentiating tumors from healthy cells in tissue is disclosed. The method includes the steps of providing a marker-folate conjugate, placing the marker-folate conjugate in contact with the tissue, and viewing the tissue.
According to another embodiment of the present invention, a method of resectioning tumor cells in tissue is provided. The method includes the steps of providing a marker-folate conjugate, exposing the tissue to the marker-folate conjugate, exposing the tissue to light, viewing the tissue, and resectioning the tissue based on the fluorescence of cells in the tissue.
According to still another embodiment of the present invention, a method of differentiating tumor cells from healthy cells in tissue is provided. The method includes the steps of providing a fluorescein-ligand conjugate, enabling contact between the fluorescein-ligand conjugate and the tissue, and viewing the tissue.
According to another embodiment of the present invention, an apparatus for differentiating tissue treated with a marker-ligand conjugate is provided. The apparatus comprises a light source configured to illuminate the tissue to cause tumor cells to appear different than healthy cells, a microscope including a lens, and a filter configured to reduce the amount of light from the light source that is transferred to the lens.
According to another embodiment of the present invention, an apparatus for differentiating in-vivo tissue treated with a marker-ligand conjugate is provided. The apparatus comprises a diffusing lens, a light source configured to emit light, the light configured to pass through the diffusing lens to illuminate the in-vivo tissue, a camera configured to receive images of the in-vivo tissue, and a filter configured to alter the amount of light that is received by the camera.
According to another embodiment of the present invention, an apparatus for differentiating in-vivo tissue treated with a marker-ligand conjugate is provided. The apparatus comprises an endoscope, a light source configured to emit light, the light configured to pass through the endoscope to illuminate the in-vivo tissue, a camera coupled to the endoscope and configured to receive images of the in-vivo tissue, and a filter configured to alter the amount of light that is received by the camera.
According to another embodiment of the present invention, a method of differentiating arthritic tissue from healthy tissue is provided. The method includes the steps of providing a marker-folate conjugate, placing the marker-folate conjugate in contact with the tissues, and viewing the tissues.
Additional features of the present invention will become apparent to those skilled in the art upon consideration of the following detailed description of the invention.